Elevation of NT-proBNP Levels in Pediatric and Young Adult Hematopoietic Stem Cell Transplant Patients with Endotheliopathy

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript suggests that NT-proBMP may serve as a potential marker for early diagnosis of endotheliopathy, a disease that can develop following HSCT in pediatric and young adult ALL patients. However, some parts may require further explanation.

1.     Line 60~63. It is said that BNT and NT-proBNP are commonly known markers associated with left ventricular dysfunction and cardiac failure, but it is recommended to explain in more detail. What is the difference between the two, and why did the authors focus on NT-proBNP in relation to HSCT, and what is the basis for it?

 

2.     Line 95~100. Is there a reason for selecting patients who developed symptoms within 100 days after transplantation? It is recommended that you explain whether there is a standard criterion and add a reference.

 3.     Line 141~145. To increase readers' understanding, briefly explain the meaning of NT-proBNP testing using estimated glomerular filtration rate (eGFP) and echocardiogram.

Author Response

Reviewer 1 - reply attached as a word document 

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors This manuscript explores the potential of using NT-proBNP as a biomarker for endotheliopathy in pediatric/AYA HSCT. Some evidence is found to support the hypothesis that NT-proBNP can serve as a biomarker in this regard; however, more research in the form of larger studies or additional indicators will be necessary. Overall, the paper is presented well reaches well-supported if underwhelming conclusions. The authors or their colleagues will want to do follow-up studies, as suggested, to establish NT-proBNP as a bona fide biomarker for endotheliopathy in pediatric/AYA HSCT.  Comments on the Quality of English Language

No significant issues

Author Response

Thank you for you appreciation and comments. Very much appreciated. 

Reviewer 3 Report

Comments and Suggestions for Authors

In this manuscript the Authors attempted to demonstrate the association between increased NT-proBNP and endotheliopathy in children and young adults undergoing stem cell transplantation. Although the study design is appropriate (case control match, primary and secondary model), the Author failed in their intent. The limited number of patients (31 in each group) is not appropriate to demonstrate the role of  NT-proBNP levels in predicting the onset of endotheliopathy. The matching criteria should be improved by also adding the type of disease as a restrictive parameter for matching.

The Authors can conclude that the NT-proBNT level increased in the near-event period, predicting the diagnosis od endotheliopathy for 2.8 days.   

The paper can be considered for publication after a thorough review of the study design and statistical analysis. 

Minor issues:

line 129: please, define "transplant protocol", autologous vs allogeneic, reduced vs standard intensity, TBI ..)

table 2: p value <0.0001 in the endotheliopathy type (first row) is not clear, specify, since there is any coparison with controls group.

Author Response

Reviewer's comments and our answers in the word document and also a word document of an updated manuscript. Will upload an updated version of manuscript after all edits are made

Author Response File: Author Response.pdf

Reviewer 4 Report

Comments and Suggestions for Authors

A retrospective case-control study found that elevated natriuretic peptide (NT-proBNP) levels were associated with the development of endotheliopathy in the first 100 days following hematopoietic stem cell transplantation (HSCT) in pediatric and young adult patients. The study found that near-event NT-proBNP levels were significantly higher in cases compared to controls, particularly in acute lymphoblastic leukemia (ALL) patients. The association between NT-proBNP and endotheliopathy did not achieve statistical significance after adjusting for covariates. However, the authors must clearly articulate a significant issue that needs resolution before a decision on the manuscript approval can be made.

 

 

Early HCT-related complications, which occur in chronological order, include sinusoidal obstruction syndrome (SOS), engraftment syndrome (ES), capillary leak syndrome (CLS), transplant-associated thrombotic microangiopathy (TA-TMA), acute graft-versus-host disease (aGvHD), and vascular idiopathic pneumonia syndrome (vascular-IPS)—including diffuse alveolar hemorrhage (DAH). These clinically relevant events share a recognized common origin in endothelial cell (EC) activation and have the potential to progress into a non-reversible multiorgan dysfunction (MOD). Thus, gaining a deeper insight into these early post-transplant complications and their relationship with the endothelium is crucial for developing effective preventive and therapeutic strategies. Nevertheless, the authors included only DAH, SOS, or TMA in the classification of endotheliopathy. I believe the title “NT-proBNP as a Biomarker of Endotheliopathy in Pediatric and Young Adult Hematopoietic Stem Cell Transplantation” requires revision; otherwise, it may be challenging to convince the reader of the conclusion. 

Author Response

Reviewer comments and our answers in the word file.

Author Response File: Author Response.pdf

Round 2

Reviewer 4 Report

Comments and Suggestions for Authors

The title has been revised to ‘NT-proBNP as a potential marker of Endotheliopathy in Pediatric and Young Adult Hematopoietic Stem Cell Transplant Patients.’ The text underwent only slight modifications, suggesting that the authors had a strong belief in the integrity of their report.

Author Response

See attached.

Author Response File: Author Response.pdf